Hydroxypyruvate reductase (HPR), a plant leaf peroxisomal enzyme in the glycolate pathway, catalyzes the conversion of hydroxypyruvate to glycerate with the oxidation of both NADH and NADPH. HPR recycles nucleotides and bases back into pathways leading to the synthesis of ATP and GTP. ATP and GTP are used to produce DNA and RNA and to control various aspects of signal transduction and energy metabolism. Transcripts of HPR are present in cotyledons and leaves. Since consumption of large quantities of fruit and vegetables is associated with a striking reduction in the risk of developing a variety of malignancies, it is of interest that a number of edible plants contain substantial quantities of compounds that regulate mammalian enzymes of xenobiotic metabolism.
Cytokinins play a critical role in the regulation and coordination of plant metabolism, growth, and morphogenesis. Altering the levels of endogenous cytokinins in transgenic plants indirectly demonstrates that cytokinins regulate gene expression. Experimental evidence indicates that there is a close association between the regulation of gene expression and cytokinin action (Chen et al. (1985) Plant Physiol. 77:99-103). One of the enzymes upregulated by the cytokinins is NADH-dependent hydroxypyruvate reductase (NHPR) from cucurbito pepo.
Inhibitors of purine nucleotide biosynthesis in general have long been employed as antiproliferative agents to treat cancer and viral diseases. It is possible to synthetically produce cytokines. Interferon (IFN), interleukin 2 (IL2), tumor necrosis factor (TNF), and haematopoietic growth factors are cytokines that have been synthesized successfully. IFN has been used in the therapy of hairy cell leukaemia, Kaposi sarcoma associated with AIDS, and metastasis of malignant melanoma. IL2 allows for an increase in the cytotoxic activity of NK cells in producing LAK cells, lymphocytes which infiltrate tumors such as malignant melanoma or carcinoma (Goy et al. (1990) Rev. Mal. Respir. 7(3):195-201).
The discovery of a new human hydroxypyruvate reductase and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of diseases associated with cell proliferation, in particular, cancers and immune response.